Research progress of cholesterol modification

<p indent="0mm">As the most abundant sterol in organisms, cholesterol plays a crucial role not only in maintaining the fluidity and integrity of cell membranes and participating in various signal transduction processes, but also as a precursor for the synthesis of important bioactive substances such as bile acids and steroid hormones. Cholesterol can undergo a variety of chemical reactions in the body, including esterification, sulfation, and nucleophilic substitution reactions involving the 3β hydroxyl group, which are important aspects of cholesterol’s involvement in physiological activities. In addition to forming cholesterol esters through covalent linkage to fatty acids, cholesterol can also modify proteins through covalent conjugation, a process that involves a series of complex biochemical reactions and plays an important role in regulating the normal function of substrate proteins. Currently, only a few proteins have been identified with cholesterylation. With the continuous progress in cholesterol modification research, this field holds promise for new breakthroughs. Furthermore, cholesterol-modifying drugs synthesized through the simulation of <italic>in vivo</italic> cholesterol modification reactions have demonstrated good therapeutic effects. Small molecule compounds that target and inhibit cholesterol modification of the Smoothened (Smo) protein can effectively kill tumor cells, while also having the advantages of overcoming drug resistance and enhancing efficacy when used in combination. Cholesterol is also used to modify small molecules, peptides, and nucleic acid drugs to increase the bioaffinity of drug molecules and improve drug stability, resulting in better therapeutic effects. This review primarily summarizes the chemical reactions involving cholesterol molecules in the body, research progress on protein cholesterylation, and research methods, while discussing the application of cholesterol modification in the field of biomedicine. The aim is to provide references for research and development in the field of cholesterol modification.